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In Vivo Aggregation of β‐Amyloid Peptide Variants
Author(s) -
Fay David S.,
Fluet Amy,
Johnson Carolyn J.,
Link Christopher D.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71041616.x
Subject(s) - thioflavin , amyloid (mycology) , peptide , in vivo , biochemistry , caenorhabditis elegans , genetically modified mouse , microbiology and biotechnology , amino acid , congo red , biology , transgene , chemistry , alzheimer's disease , gene , genetics , pathology , medicine , disease , organic chemistry , adsorption , botany
Transgenic Caenorhabditis elegans animals have been engineered to express wild‐type and single‐amino acid variants of a long form of human β‐amyloid peptide (Aβ 1–42). These animals express high levels (∼300 ng of Aβ/mg of total protein) of apparently full‐length peptide, as determined by quantitative immunoblot. Expression of wild‐type Aβ in these animals leads to rapid production of amyloid deposits reactive with Congo red and thioflavin S. This model system has been used to examine the effect of Leu 17 Pro, Leu 17 Val, Ala 30 ‐Pro, Met 35 Cys, and Met 35 Leu substitutions on the in vivo production of amyloid deposits. We find that the Leu 17 Pro and Met 35 Cys substitutions completely block the formation of thioflavin S‐reactive deposits, implicating these as key residues for in vivo amyloid formation. We have also constructed transgenic strains expressing a novel Aβ variant, the single‐chain dimer. Animals expressing high levels of this variant also fail to produce thioflavin S‐reactive deposits.